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Could coffee be a wake-up cure for neurodegeneration?

A morning routine is a unique experience. While some naturally rise with the sun others hit snooze repeatedly; vowing to never stay up binging an entire Netflix series again. But whether you are an early or not-so-early bird, one action is pretty unanimous in the pre-work-up prep: coffee. The caffeinated beverage which can be drank hot or cold, sipped or shotted, black or white, seated or to go, with a general purpose to boost your alertness first thing in the a.m. But have you ever thought about how coffee acts on your brain to make you feel fast instead of fatigued? And what about the long-term consequences of your consumption of Joe on your neurons and co? Research into the action of caffeine, other active chemicals in coffee and the brain have uncovered interesting links between coffee and cognition, including lessening neurodegenerative diseases (*a clickbait article enters cyberspace*). But just how true are the claims that drinking coffeee is neuro-protective?

The Chemistry of Coffee

When you request your venti flat white with soya milk and sugar-free vanilla syrup, the barrister in Starbucks may seem like a wizard; concocting the perfect cup of poison to send that much-needed wake-up call to your brain. You are not wrong for feeling like sipping the life-giving liquid is a magical experience as brewing coffee is just like a potions class. Each little bean which goes into your cup contains a particular blend of chemicals which gives coffee its smell, taste and, most importantly, its kick. The A+ conical of coffee contains 1000s of different chemicals which contribute towards it’s aroma, known-antioxidant compounds called chlorogenic acids as well as the stimulating caffeine. In isolation, some of coffee’s chemicals are supposedly able to induce ‘drunk states’ in rats (2-Ethylphenol) and treat symptoms of asthma (Theophylline). Despite the complex actions of the many compounds present in coffee, the dose received in a single cup aren’t quite up to rendering you above the driving limit.

Once you gulp down your hot concoction, some of the coffee chemicals are able to pass from your digestive system into your blood and up to your brain, and the chemical responsible for exerting an alertness effect is caffeine. Caffeine (aka 1,3,7-trimethylxanthine - so catchy) wakes you up by binding to receptors on the surface of neurons which normally bind a chemical called adenosine. Adenosine is a chemical compound which builds up in your brain throughout the day and binds to adenosine receptors to inform neurons of your tiredness. Then more adenosine bound, the sleepier you feel until you are so overcome with tiredness, you fall asleep. Overnight, this adenosine is cleared and the build-up can begin again the next day. Caffeine competes with adenosine to bind to some of these receptors in the brain, and when caffeine latches on, it stops ‘sleepiness' signals being sent. Caffeine can hang around in the body for hours after finishing your cup so having a late-evening latte might disrupt your sleep - with adenosine waiting in the wings for caffeine clearance before being able to take you off to the land of nod.

Cognition and Caffeine

As coffee is such a widely-consumed, physco-active beverage, the effect it has over time on your brain has been studied in human populations and in laboratory set-ups. Too much caffeine in one sitting is correlated with unpleasant actions such as anxiety-like behaviours and headaches, which you will know if you’ve had to pull an all nighter before a deadline and used an excess of coffee to keep sleepy-time at bay. However, high intake of coffee over time has been associated with some cognitive benefits in several studies, including enhanced working memory in rats when they were fed approximately 10 cups worth of coffee per day. Similar relationships have been drawn in large-scale studies of people who consume high levels of caffeinated drinks, however other human studies have reported no such relationship. Isolating the effects of coffee when its intake is ingrained into everyday life amongst a myriad of other influential variants, such as diet, is tricky. Plus, coffee’s known short-term impact on alertness, arousal and mood could also contribute to a temporary elevation in working memory rather than actually enhancing long-term memory potential.

Research has also focused on the impact of coffee intake and the development of disease, including disorders of the brain. In two studies published over the past year, the relationship between specific chemicals in coffee and their potentially alleviating affects on neurodegenerative-associated mechanisms have been explored. Research by scientists at the University of Toronto found phenylindane, a compound in coffee, was capable of reducing the aggregation of Alzheimer’s disease associated proteins (amyloid-beta and tau) in the lab. Large protein aggregates in the brain are a hallmark of many neurodegenerative disease, therefore a hypothesised therapeutic mechanism is to prevent this aggregation happening; and a coffee compound looks like it can do that in a dish. Further to this bench-top work, another research group from Rutgers Robert Wood Johnston Medical School assessed the therapeutic impact of co-administering Eicosanoyl-5-hydroxytryptamide (EHT), another coffee-chemical, and caffeine to mice which present with Parkinson’s-like symptoms and a-synuclein pathologies, seen in Parkinson’s patients, later in their lifespan. The results of the experiment showed giving the animals EHT and caffeine lead to improved behavioural performance of these mice as well as amelioration of some of the pathological hallmarks they usually acquire with age by ’switching off’ a specific gene (PP2A). This lead to a conclusion that coffee has the potential to prevent the Parkinson’s-mediated neurotoxicity.

Could coffee intake reduce neurodegeneration?

Studies such as those above do imply there are chemicals in coffee which could protect against mechanisms we believe to be crucial in neurodegenerative cascades. However, conclusions cannot be jumped to. Both of these studies were not done in human’s. The first was performed with pure protein in test tubes, which while good for testing protein-protein interactions, cannot inform us of the physiological interactions between these proteins when in the human brain - a completely different chemical environment. Although the second study was done in mice, representing a more ‘real’ environment for these interactions, the mice were genetically modified to hugely over-express a-synuclein - a non-physiological phenomenon which could alter the way proteins in the brain interact. Laboratory tests are vital in these types of studies, but strong conclusions cannot be made until mechanisms are confirmed in humans.

In addition, the dose of ‘coffee’ will also hugely impact these potentially-protective interactions. A favourite saying of the amazing Insta-chemists I interact with is ‘the poison is in the dose’ and the same concept applies to reducing pathological events using chemicals. In the mouse study above, mice were fed 50mg/kg of caffeine per day. If you translate this into human weight, I, a 59kg woman, would have to get almost 3000 mgs of caffeine per day - equating to over 30 cups of average coffee (95mg of caffeine per cup). Unless I want to be a shaking mess, there is no chance I am coming close to 30 cups of coffee each day. A lot of these studies hugely up the 'regular’ dose - which is fine for proving an interaction has the potential to happen and cause an effect, but physiologically, this is a lot harder to interpret.

Finally, we are still not 100% sure on what mechanisms cause neurodegeneration. Both of these studies rely on the hypothesised mechanisms of protein aggregates found in the diseases being causative agents in mediating neurodegeneration. Caffeine and other coffee-based chemicals may interact with these aggregate-forming proteins and even prevent their formation, but we still do not know if this would definitely help stop neurodegeneration. Plus, as mentioned, other factors such as diet and genetics could vary our response to coffee’s mechanisms within the brain. This research points towards a potentially positive effect on caffeine intake and neuroprotection but many more large-scale, properly controlled human studies need to be conducted before we can stamp the neuroprotective label on this well-loved beverage.

Overall, when you read coffee-based research, leave the sugar and take your joe with a pinch of salt.




A splash of extra reading

Main Papers

Mancini et al (2018). Phenylindanes in Brewed Coffee Inhibit Amyloid-Beta and Tau Aggregation. Front. Neurosci. Vol 12.

Yan et al (2018). Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson's disease and DLB. PNAS. 115 (51)

Background Lit

The Chemistry in every cup

Here's everything that's hiding in your cup of coffee

A review of caffeine’s effects on cognitive, physical and occupational performance

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants

Is caffeine a cognitive enhancer?

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